Radiologic findings of osteonecrosis, osteoradionecrosis, osteomyelitis and jaw metastatic disease with cone beam CT.

PURPOSE: The purpose of this study was to assess CBCT scans of patients with medication related osteonecrosis of the jaws (MRONJ), osteoradionecrosis (ORN), osteomyelitis (OM) and jaw metastatic disease (JM), evaluate the presence and extent of radiologic findings, identify radiologic parameters that may distinguish the four entities and last, introduce a new modified radiographic index (CRIm), in order to contribute to the diagnosis of these conditions. METHODS: Τwo major databases were retrospectively searched for fully documented and diagnosed CBCT scans of MRONJ, ORN, OM and JM from 2006 to 2019. 335 CBCT scans met the inclusion criteria and were assessed under standardized viewing conditions blindly by 2 observers. The CRIm index proposed in this study evaluates: lytic changes, sclerosis, periosteal bone formation, sequestration, non-healing extraction sockets and other findings which included: sinus implication, inferior alveolar canal implication and jaw fracture. Lytic changes, sclerosis, periosteal bone formation, sequestration and non-healing extraction sockets were scored as: absent (0), localized/single (1) and extensive/multiple (2). Each one of other findings were scored individually as: absent (0) and present (1). For statistical analysis t-test, Pearson's r correlation coefficient, one-way ANOVA and Bonferonni were performed. RESULTS: Extensive lytic changes were the most common finding, especially for ORN, where it occurred in all CBCT scans (100%). The mean value of the CRIm index differs significantly between CBCT scans with MRONJ and JM, as well as between those with OM and JM (Bonferroni p < 0.001). CONCLUSIONS: The new modified Composite Radiographic Index introduced in this study, appears to have improved an objective approach to the previously used Composite Radiographic Index by means of cumulative radiologic features. Τhe predominance of certain radiologic features in one or more of these entities may lead the diagnostician towards the correct diagnosis.

Co-existence of Congenital Epidermoid Cyst and Ranula in a Newborn. Report of a Unique Case.

Background: Congenital cystic swellings involving the floor of the mouth include various lesions such as developmental cysts (e.g., dermoid and epidermoid cysts), ranulas, vascular malformations etc. However, coexistence of such conditions, possibly with a cause-and-effect- relationship, is rare. The purpose of this case report is to present a rare case of a congenital epidermoid cyst associated with a mucous retention cyst in a newborn. Methods: A 6-month-old female infant was referred to an Oral Medicine Clinic in Athens, Greece on October 2019 for evaluation of a swelling at the floor of the mouth, first noticed by her paediatrician just after birth. Clinically, a yellowish "pearly" nodule in close association with the orifice of the left submandibular duct, posteriorly transitioning to a diffuse bluish cystic swelling of the left floor of the mouth was observed. With a provisional diagnosis of a dermoid cyst and/or ranula, a surgical excision was performed under general anaesthesia. Results: Histopathologically, a well-defined, keratin-filled, cystic cavity lined by orthokeratinized stratified squamous epithelium was observed in the anterior aspect while posteriorly and in close proximity, a dilated salivary duct lined by cylindrical, cuboidal or pseudostratified epithelium was noted. A final diagnosis of an epidermoid cyst intimately associated with a mucus retention cyst (ranula) of the submandibular duct was rendered. Conclusions: The coexistence of two cystic lesions in the floor of the mouth with features of epidermoid and mucous retention cyst, respectively, is rare and its pathogenesis intriguing, especially in a newborn.

Plasma Cell Gingivitis and Its Mimics.

Plasma cell gingivitis (PCG) is an inflammatory condition that affects the gingival mucosa of the oral cavity. It is characterized by polyclonal dense plasma cell infiltrate in the connective tissue. Lesions do not respond to prophylactic treatment. Etiology is most likely hypersensitivity to certain antigens (eg, toothpastes, oral rinses, chewing gums, spices). Differential diagnosis of PCG includes reactive, granulomatous, and neoplastic lesions. The diagnostic workup is based on patient's history and the clinicopathologic correlation to rule out mimics of PCG. Dermatologic patch test may be indicated in chronic conditions to identify the allergen.

Cheilitis Glandularis: A clinicopathologic study with emphasis on etiopathogenesis.

OBJECTIVES: Cheilitis Glandularis (CG) is an uncommon entity of obscure etiology. A cases series is presented with emphasis on etiopathogenesis. MATERIALS AND METHODS: Fourteen CG cases were analyzed according to their demographic and clinicopathologic characteristics. RESULTS: The mean age of the patients with CG was 68.1 years, while a male-to-female ratio of 1.8:1 was observed. One or more potential causative factors were identified for each patient, including long-term smoking (9 cases), xerostomia (4 cases), cosmetic filler injections (2 cases), and actinic cheilitis (1 case). The lesions were located on the lips, buccal mucosa, or both in 7, 2, and 5 cases, respectively. Multiple submucosal nodules with dilated ductal orifices and mucous or purulent discharge were observed in all cases. Histopathologically, ductal ectasia with metaplasia, intraductal mucin, and chronic or mixed inflammation were noted, as well as pools of hyaluronic acid in 2 cases with a history of cosmetic filler injections. CONCLUSIONS: CG etiopathogenesis is probably multifactorial. Reduced salivary flow rate and increased viscosity of saliva, potentially caused by long-term smoking, diabetes mellitus, and drug-induced xerostomia, may participate in the initial pathogenesis, while local irritants, for example, poor oral hygiene and local trauma, may further contribute to the development and aggravation of the condition.

Prognostic outcomes of oral squamous cell carcinoma derived from proliferative verrucous leukoplakia: A systematic review.

OBJECTIVE: This study aimed to evaluate prognostic outcomes of PVL-derived oral squamous cell carcinomas (P-OSCC) based on recurrence, new primary tumour, metastasis and survival information. STUDY DESIGN: Five databases and grey literature were searched electronically with the following main keywords (proliferative verrucous leukoplakia, squamous cell carcinoma and malignant transformation) to answer the following review question: 'Are survival outcomes for P-OSCC worse?' based on the PECOS principle. The Joanna Briggs Institute Critical Appraisal tool was used to identify possible biases and assess the quality of each of the primary studies. RESULTS: A total of 21 articles met the inclusion criteria, and the results of this systematic review suggest that P-OSCC can recur and generate new primary tumours; however, metastases are rare. Thus, most patients remain alive for an average period of 5 years. CONCLUSION: Apparently, P-OSCC has better clinical prognostic characteristics than conventional OSCC. There is a lack of information on the main prognostic outcomes of P-OSCC; therefore, specific studies must be performed to achieve a better comparison between P-OSCC and conventional OSCC progression.

Oral Side Effects in Patients with Metastatic Renal Cell Carcinoma Receiving the Antiangiogenic Agent Pazopanib-Report of Three Cases.

Pazopanib is a potent multi-kinase inhibitor that hinders angiogenesis and blocks tumor growth. It has been approved for the treatment of metastatic renal cell carcinoma (mRCC) and advanced soft tissue sarcoma. There is emerging evidence that bleeding is a common adverse effect of pazopanib and other targeted therapies in patients with mRCC. In addition, jaw osteonecrosis related to pazopanib was recently described in the literature. We report three cases of patients with mRCC who developed adverse oral events related to pazopanib. The first patient, treated with pazopanib as monotherapy, presented with gingival bleeding and oral burning sensation. The other two patients receiving pazopanib as monotherapy and pazopanib followed by sunitinib, respectively, presented complaining about mandibular pain; a diagnosis of medication-related osteonecrosis of the jaw (MRONJ) was rendered in both cases. Gingival bleeding and MRONJ may develop as oral side effects of pazopanib use. The cases presented here aim to alert and inform health care professionals about the risk of adverse oral events in patients with mRCC receiving the antiangiogenic agent pazopanib.

Lymphoepithelial Subtype of Oral Squamous Cell Carcinoma: Report of an EBV-Negative Case and Literature Review.

Lymphoepithelial carcinoma (LEC) of the oral mucosa is a rare histopathologic subtype of squamous cell carcinoma (SCC), which shares morphologic similarities with nasopharyngeal carcinoma (NPC), non-keratinizing undifferentiated subtype. The admixture of neoplastic epithelial tumor cells and a dense lymphoplasmacytic infiltrate makes microscopic diagnosis challenging. LEC etiopathogenesis has been variably associated with Epstein-Barr virus (EBV) infection, depending on the specific anatomic location and racial predilection, with a higher incidence in endemic populations. Although described in several subsites of the head and neck region, including the major salivary glands, the oral mucosa is considered an infrequent location for LEC development, deriving either from minor salivary glands (MSGs) or the surface epithelium. Herein, we report a rare case of an EBV-negative LEC arising from the oral surface epithelium, presenting as gingival swelling, and review the pertinent English-language literature, which revealed only 26 previously reported oral LECs. Our case is only the fourth oral LEC originating from the surface epithelium and the first one to affect the gingiva.

Expression of BMP4 and FOXN1 in orthokeratinized odontogenic cyst compared to odontogenic keratocyst suggests an epidermal phenotype.

Odontogenic keratocysts (OKC) and orthokeratinized odontogenic cysts (OOC) are odontogenic cysts that share histological and immunohistochemical similarity with epidermal appendages and cutaneous cystic lesions despite exhibiting contrasting biological behavior. In epidermal appendages, BMP4 induces expression of FOXN1, which participates in terminal differentiation of keratinocytes and control of proliferation. We compared BMP4 and FOXN1 expression in OOC and OKC to investigate their role in the epithelial differentiation of these cysts. BMP4 and FOXN1 expression was assessed using immunohistochemistry in 20 primary sporadic OKC and compared to 16 OOC. BMP4 epithelial expression was detected in 81.25% OOC compared to 35% in OKC, while its expression in connective tissue was observed in 65% OKC and 75% OOC. FOXN1 was detected in 75% OOC vs. 30% OKC. The "triple positive" phenotype, i.e., BMP4 epithelial and connective tissue positivity and FOXN1 epithelial positivity, was seen in 56.25% OOC compared to 10% OKC. The greater expression of BMP4 and FOXN1 in OOC suggests greater activation of this pathway in OOC, which suggests a role in its more mature epithelium; it also resembles an epidermal phenotype.

Base of tongue metastasis of cutaneous malignant melanoma with rhabdoid and neuroendocrine features: Report of a rare case and review of the literature.

Metastatic malignant melanoma (MM) represents a highly aggressive cancer associated with overall poor prognosis. Various anatomic sites can be affected, including the oral cavity and the oropharynx. It may mimic other entities by assuming a variety of clinical appearances and exhibiting a plethora of microscopic variations. Herein, we present a case of a 63-year-old male with a MM metastasizing to the base of tongue, which developed 5 years after the original diagnosis and treatment of cutaneous MM of the chest and heralded its relapse; subsequently, neurological symptoms developed as a result of metastasis to the brain. Diagnostic challenges were encountered, as the tongue lesion clinically masqueraded as a pedunculated reactive lesion and microscopically displayed unusual rhabdoid and neuroendocrine features. Tumor cells expressed S-100, HMB-45, Melan-A, and SOX-10, while most cells with rhabdoid morphology were also positive for myogenin and Myo-D1. Chromogranin and synaptophysin positivity was further noticed in a subset of cells, suggestive of focal neuroendocrine differentiation. Molecular investigation revealed mutations for the BRAF V600E gene. Divergent differentiation of tumor cells may cause diagnostic pitfalls necessitating thorough immunohistochemical analysis. The presence of rhabdoid features and neuroendocrine differentiation are very uncommon, while their co-existence is extremely rare. Better characterization of such microscopic variations in MMs with evaluation of their potential biologic significance is warranted.

Scleroderma-specific autoantibodies: Should they be included in the diagnostic work-up for Sjögren's syndrome?

OBJECTIVES: Sicca complaints are a frequent reason for rheumatologic consultation. Testing for specific antibodies against Ro/SSA and La/SSB antigens and minor salivary gland (MSG) biopsy are among the main tools implemented in the diagnostic work-up. Anticentromere antibodies and sicca manifestations are frequently detected in Sjögren's syndrome (SS) and systemic sclerosis (SSc), respectively. Herein, we aimed to determine the frequency and clinical associations of a wide spectrum of scleroderma (SSc)-specific autoantibodies in consecutive patients referred for evaluation of possible SS. METHODS: Demographic, clinico-pathological, and laboratory data were recorded in 216 consecutive patients with sicca complaints. All study participants were tested for SSc-specific autoantibodies (against CENP, PM/Scl, Scl-70, Ku, NOR90, RP11, RP155, fibrillarin, PDGFR, and Th/To) using a commercially available immunoblot kit. According to band intensity, the identified autoantibodies were further classified in those with strong and medium titers. RESULTS: SSc-specific autoantibodies were detected in 41.7% (90/216) patients evaluated (19% at strong, 22.7% at medium titers) without significant differences between anti-Ro/SSA positive and negative groups. At strong titers was significantly higher in patients with MSG biopsies fulfilling SS histopathological criteria (30% vs 12.5%, p = 0.009). This association remained significant after adjustment for antibodies against Ro/SSA and La/SSB autoantigens [OR 95% (CI): 4.1 (1.5-10.6)]. CONCLUSION: SSc-specific autoantibodies are frequently detected among patients presenting with sicca complaints and at strong but not medium titers are independently associated with MSG biopsy positivity. Taken together, these data imply a useful role of SSc antibody testing in the diagnostic work-up and possibly in the classification criteria for SS.

Acquired Compound Melanocytic Nevus on the Palate of a Child: Report of a Case.

Background: Oral melanocytic nevi are relatively rare in comparison to their cutaneous counterparts. The aim of this manuscript is to present a case of acquired compound oral melanocytic nevi on the hard palatal mucosa of a child. Methods: A 5-year-old female girl was referred for evaluation of a pigmented lesion on the hard palate. The lesion was asymptomatic and present for approximately 2 months. Oral clinical examination revealed a well-circumscribed brownish macule on the hard palatal mucosa, adjacent to the left first primary upper molar. Considering the recent onset of the lesion, biopsy was recommended, but the patient returned 3 years later, when increase in size with slight asymmetry and colour variation were noticed. An excisional biopsy was performed. Results: Microscopic examination revealed nevus cells randomly distributed along the basal cell layer and organized into nests along the junctional area and within the papillary layer of lamina propria, while immunohistochemical evaluation showed positivity of nevus cells for SOX-10 and Melan-A. A final diagnosis of compound melanocytic nevi was rendered, and the patient was advised to attend regular follow-up appointments. Conclusions: Although oral melanocytic nevi are rare in childhood, their potential development should not be overlooked. Acquired oral melanocytic nevi need to be differentiated from several other common (e.g. amalgam tattoo) and uncommon (e.g. melanoma) oral pigmented lesions, as well as from the more rare congenital oral melanocytic nevi. Oral melanocytic nevi with junctional activity (i.e. junctional, compound subtypes) appear to be more common in children, possibly reflecting an earlier developmental stage.

Diagnostic challenges in a diffuse large B-cell lymphoma of the maxilla presenting as exposed necrotic bone.

Lymphoma is the second most common malignancy in the head and neck area, affecting both nodal and extranodal sites, including oral soft and hard tissues, usually in the form of non-Hodgkin's lymphoma (NHL). However, lymphomas of the jaws, including diffuse large B-cell lymphoma (DLBCL), the most common type of NHL, are very rare and may cause significant diagnostic challenges resembling common jaw pathologies, such as periapical lesions, osteomyelitis and osteonecrosis. The aim of this paper is to present a rare case of DLBCL in an 84-years-old diabetic male patient on methylprednisolone treatment for autoimmune hemolytic anemia. The lesion appeared clinically as exposed necrotic bone of the maxilla with surrounding soft tissue ulceration and radiographically as an extensive osteolytic lesion with ill-defined borders. Despite the resemblance of the lesion with osteonecrosis or osteomyelitis that could be theoretically related to diabetes and/or systemic use of corticosteroids, histopathologic examination, necessitating a repeat biopsy in order to acquire sufficient tissue, revealed the final diagnosis of lymphoma. The need for increased clinical awareness and vigilance of this possible diagnostic conundrum is emphasized. Key words:Diffuse large B-cell lymphoma, exposed bone, oral, malignancy, maxilla, jaw osteonecrosis, differential diagnosis.

The oral mycobiome: Oral epithelial dysplasia and oral squamous cell carcinoma.

Fungi, a diverse group of eukaryotic organisms, play distinct roles in health and disease. Recent advances in the field of mycobiology have enabled the characterization of the "human mycobiome." The human mycobiome has extensively been studied in various disease models. However, to date, the role of the oral mycobiome in oral carcinogenesis has yet to be elucidated. Candida albicans, the most common oral colonizer, has been speculated to display tumorigenic effects; however, the literature lacks consistent documentation from mechanistic studies on whether oral mycobiota act as drivers, facilitators, or passive colonizers of oral premalignancy and cancer. This review article provides an overview of existing hypothesis-driven mechanistic models that outline the complex interplay between the oral mycobiome and oral epithelial dysplasia as well as their potential clinical implications.

Juvenile trabecular ossifying fibroma: Immunohistochemical expression of MDM2, CDK4 and p53 compared to conventional ossifying fibroma.

BACKGROUND: Juvenile ossifying fibroma (JOF) is an uncommon benign fibro-osseous lesion of the craniofacial skeleton; compared to conventional ossifying fibroma (OF), JOF is characterized by local aggressiveness and propensity for recurrence. The biologic basis for this different biologic behavior between JOF and OF remains elusive. The aim of this study was to evaluate the immunohistochemical expression of MDM2, CDK4 and p53, molecules associated with bone oncogenesis, in the trabecular variant of JOF. MATERIAL AND METHODS: The study material consisted of five cases of trabecular JOF, affecting three male and two female patients with a mean age of 11.8 years. Three cases arose in the maxilla and two in the mandible. All cases were initially treated by enucleation; two cases recurred necessitating more aggressive treatment. Immunohistochemical study of MDM2, CDK4 and p53 was performed in all cases, as well as in five control cases of conventional OF. RESULTS: CDK4 positivity was noted in all JOF cases; the staining pattern was diffuse and strong in 4 cases and focal and weak in one case. In contrast, 4 out of 5 cases of OF were weakly and focally CDK4 positive, the remaining one being negative. Immunostaining for MDM2 was observed in 3 JOF cases; all OF were MDM2 negative. All cases of OF and JOF were negative for p53, except for one focally positive JOF case. CONCLUSIONS: CDK4 and MDM2 expression in the trabecular variant of JOF is higher compared to conventional OF. In contrast, p53 expression is almost universally negative in JOF and OF. Despite some overlapping features, differential expression patterns of proteins involved in bone oncogenesis can elucidate the pathogenesis and may facilitate accurate diagnosis and prediction of behavior of bone tumors in the craniofacial region. Key words:Juvenile ossifying fibroma, trabecular variant, conventional ossifying fibroma, MDM2, CDK4, p53.

Aplasia of the Major and Minor Salivary Glands: Report of a Rare Case.

Background: Aplasia of the salivary glands, either partial or involving all the major and possibly the minor salivary glands, is a very rare cause of hyposalivation. The aim of this case report is to present a case of aplasia of the major and minor salivary glands and discuss the relevant literature. Methods: A 23-year-old woman, with a non-contributory medical and family history was referred due to rampant caries, that could not be attributed to any obvious aetiology. No sicca symptoms, previous parotid gland swelling or general symptoms were reported. Clinically, oral mucosa dryness and extended dental erosions and caries were observed, while the orifices of the excretory ducts of the parotid and submandibular salivary glands were not evident. Unstimulated and stimulated saliva flow rates were severely diminished, while a diagnostic biopsy of the lower lip revealed absence of minor salivary glands. Detailed hematologic and immunological investigations to exclude systemic disorders were also within normal limits. Ultrasound and magnetic resonance imaging revealed the absence of all major salivary glands, confirming the clinical diagnosis of congenital aplasia of the salivary glands. Results: Oral hygiene instructions and dietary advice were given while dental products with fluoride and saliva substitutes were administered and appropriate dental treatment was implemented. Regular dental follow-up was also advised. Conclusions: Timely diagnosis of aplasia of the salivary glands is important, considering the detrimental effects of the absence of saliva on oral health. Management consists of the use of saliva substitutes, nutritional adaptation, maintenance of oral health and regular dental follow-ups.

Chronic Osteomyelitis With Proliferative Periostitis of the Mandible in a Child: Report of a Case Managed by Immunosuppressive Treatment.

BACKGROUND: Osteomyelitis with proliferative periostitis is a relatively uncommon inflammatory condition of the jaws, mainly characterized by periosteal formation of reactive bone. It primarily affects children and adolescences, also referred to as Garre's osteomyelitis, more frequently involving the molar region of the mandible. Cases lacking an obvious source of infection may have an immunologically mediated etiopathogenesis, falling under the spectrum of primary chronic osteomyelitis or chronic recurrent multifocal osteomyelitis (CRMO). CASE REPORT: Herein, we present a case of chronic osteomyelitis in a 6.5-year-old girl, who suffered from recurrent painful episodes of swelling of the mandible for the last 2 years, previously requiring hospitalization and administration of intravenous (IV) antibiotics and NSAIDs with limited responsiveness. The biopsy showed features consistent with osteomyelitis with proliferative periostitis. The patient was initially managed with an IV combination antibiotic regimen with only partial improvement. The possibility of an autoimmune mechanism in the context of primary chronic osteomyelitis or CRMO was considered, and immunosuppressive therapy (TNF inhibitor etanercept along with corticosteroids and methotrexate) was administered, resulting in clinical resolution. CONCLUSIONS: Osteomyelitis and its childhood variants are relatively rare and their management presents several challenges. Although typically treated with administration of antibiotics, possibly along with surgical intervention, other treatment modalities may be necessary for resilient and persistent cases. In a subset of cases, especially in the absence of local infectious factors, immunologically mediated mechanisms may play an important role and appropriate immunosuppressive therapy may be effective.

Blastoid Mantle Cell Lymphoma of the Palate: Report of a Rare Aggressive Entity and Review of the Literature.

Mantle cell lymphoma (MCL) is a well-defined, non-Hodgkin lymphoma of B-cell origin displaying diverse morphological phenotypes and variable disease course. The World Health Organization recognizes two aggressive histopathologic variants of this type of lymphoma: pleomorphic and blastoid MCL. To date, only few cases of MCL affecting the oral cavity have been reported. Additionally, the involvement of the oral and maxillofacial area by aggressive MCL subsets is considered extremely rare with only two patients reported in the English language literature to the best of our knowledge. Herein, we describe a 69 year-old male with a prior history of MCL of the right lateral pharyngeal wall developing a recurrent lesion extending to the palatal mucosa as diffuse ulceration and exhibiting histomorphological features of blastoid MCL. We also review the pertinent literature with emphasis on the diagnostic challenges and distinction between the different MCL variants.

Understanding the complex pathogenesis of oral cancer: A comprehensive review.

The pathogenesis of oral cancer is a complex and multifactorial process that requires a deep understanding of the underlying mechanisms involved in the development and progress of malignancy. The ever-improving comprehension of the diverse molecular characteristics of cancer, the genetic and epigenetic alterations of tumor cells, and the complex signaling pathways that are activated and frequently cross talk open up promising horizons for the discovery and application of diagnostic molecular markers and set the basis for an era of individualized management of the molecular defects underlying and governing oral premalignancy and cancer. The purpose of this article is to review the key molecular concepts that are implicated in oral carcinogenesis, especially focusing on oral squamous cell carcinoma, and to review selected biomarkers that play a substantial role in controlling the so-called "hallmarks of cancer," with special reference to recent advances that shed light on their deregulation during the different steps of oral cancer development and progression.

Recurrence in Oral Premalignancy: Clinicopathologic and Immunohistochemical Analysis.

Oral leukoplakia (OL) has a propensity for recurrence and malignant transformation (MT). Herein, we evaluate sociodemographic, clinical, microscopic and immunohistochemical parameters as predictive factors for OL recurrence, also comparing primary lesions (PLs) with recurrences. Thirty-three patients with OL, completely removed either by excisional biopsy or by laser ablation following incisional biopsy, were studied. Selected molecules associated with the STAT3 oncogenic pathway, including pSTAT3, Bcl-xL, survivin, cyclin D1 and Ki-67, were further analyzed. A total of 135 OL lesions, including 97 PLs and 38 recurrences, were included. Out of 97 PLs, 31 recurred at least once and none of them underwent MT, during a mean follow-up time of 48.3 months. There was no statistically significant difference among the various parameters in recurrent vs. non-recurrent PLs, although recurrence was most frequent in non-homogeneous lesions (p = 0.087) and dysplastic lesions recurred at a higher percentage compared to hyperplastic lesions (34.5% vs. 15.4%). Lower levels of Bcl-xL and survivin were identified as significant risk factors for OL recurrence. Recurrences, although smaller and more frequently homogeneous and non-dysplastic compared to their corresponding PLs, exhibited increased immunohistochemical expression of oncogenic molecules, especially pSTAT3 and Bcl-xL. Our results suggest that parameters associated with recurrence may differ from those that affect the risk of progression to malignancy and support OL management protocols favoring excision and close monitoring of all lesions.